Aberrant gene expression in affected tissue as compared to normal tissue is a common characteristic of many human diseases. This is true for cancer and many neurological diseases which are characterized by changes in gene expression patterns. Gene expression patterns are controlled at multiple levels in the cell. Control of gene expression can occur through modifications of DNA: DNA promoter methylation is associated with suppression of gene expression. Several inhibitors of DNA methylation are approved for clinical use including the blockbuster Vidaza™. Another class of modifications involve histones which form the protein scaffold that DNA is normally associated with (coiled around) in eukaryotic cells. Histones play a crucial role in organizing DNA and the regulated coiling and uncoiling of DNA around the histones is critical in controlling gene expression—coiled DNA is typically not accessible for gene transcription. A number of histone modifications have been discovered including histone acetylation, histone lysine methylation, histone arginine methylation, histone ubiquinylation, and histone sumoylation, many of which modify accessibility to the associated DNA by the cells transcriptional machinery. These histone marks serve to recruit various protein complexes involved in transcription and repression. An increasing number of studies are painting an intricate picture of how various combinations of histone marks control gene expression in cell-type specific manner and a new term has been coined to capture this concept: the histone code.
The prototypical histone mark is histone acetylation. Histone acetyl transferase and histone deacetylases are the catalytic machines involved in modulation of this histone mark although typically these enzymes are parts of multiprotein complexes containing other proteins involved in reading and modifying histone marks. The components of these protein complexes are typically cell-type specific and typically comprise transcriptional regulators, repressors, co-repressors, receptors associated with gene expression modulation (e.g., estrogen or androgen receptor). Histone deacetylase inhibitors alter the histone acetylation profile of chromatin. Accordingly, histone deacetylase inhibitors like Vorinostat (SAHA), Trichostatin A (TSA), and many others have been shown to alter gene expression in various in vitro and in vivo animal models. Clinically, histone deacetylase inhibitors have demonstrated activity in the cancer setting and are being investigated for oncology indications as well as for neurological conditions and other diseases.
Another modification that is involved in regulating gene expression is histone methylation including lysine and arginine methylation. The methylation status of histone lysines has recently been shown to be important in dynamically regulating gene expression.
A group of enzymes known as histone lysine methyl transferases and histone lysine demethylases are involved in histone lysine modifications. One particular human histone lysine demethylase enzyme called Lysine Specific Demethylase-1 (LSD1) was recently discovered1 to be involved in this crucial histone modification. LSD1 has a fair degree of structural similarity, and amino acid identity/homology to polyamine oxidases and monoamine oxidases, all of which (i.e., MAO-A, MAO-B and LSD1) are flavin dependent amine oxidases which catalyze the oxidation of nitrogen-hydrogen bonds and/or nitrogen carbon bonds. LSD1 has been recognized as an interesting target for the development of new drugs to treat cancer, neurological diseases and other conditions.
Cyclopropylamine containing compounds are known to inhibit a number of medically important targets including amine oxidases like Monoamine Oxidase A (MAO-A; or MAOA), Monoamine Oxidase B (MAO-B; or MAOB), and Lysine Specific Demethylase-1 (LSD1). Tranylcypromine (also known as 2-phenylcyclopropylamine), which is the active ingredient of Parnate® and one of the best known examples of a cyclopropylamine, is known to inhibit all of these enzymes. Since MAO-A inhibition may cause undesired side effects, it would be desirable to identify cyclopropylamine derivatives that exhibit potent LSD1 inhibitory activity while being devoid of or having substantially reduced MAO-A inhibitory activity.
Compounds which act as inhibitors of LSD1 are known in the art. LSD1 inhibitors and methods for making them are for example disclosed in WO 2011/1316972, WO 2012/1351133, WO 2013/0573224, WO 2010/1435825, WO 2011/1315766, WO 2013/0220477, WO 2013/0258058, WO 2014/0580719, WO 2014/08429810, WO 2014/08561311, WO 2014/08679012, WO2014/16486713, WO 2014/19428014, WO 2014/20521315, WO 2015/02112816, WO 2015/03156417, WO 2015/08919218, WO 2015/12028119, WO 2015/12346520, WO 2015/12343721, WO 2015/12342422, WO 2015/12340823, WO 2015/13497324, WO 2015/15641725, WO 2015/168466, WO 2015/181380, WO 2015200843, WO 2016003917, WO 2016/00410526, WO 2016/00772227, WO 2016/00772728, WO 2016/00773129, WO 2016/00773630, WO 2016/03494631, WO 2016/03700532, CN 10554180633, WO 2016/12338734, WO 2016/13095235, CN 10592436236, CN 10598526537, WO 2016/16128238, CN 10604586239, CN 10604588140, WO 2016/17249641, WO 2016/17765642, WO 2017/00451943, WO 2017/02767844 which are incorporated in their entirety herein.
WO 2012/1351133 discloses compounds, for example GSK2879552 [CAS Reg. No. 1401966-69-5], also known as 4-[[4-[[[(1R,2S)-2-phenylcyclopropyl]amino]methyl]-1-piperidinyl]methyl]-benzoic acid (Example 26 on p. 75, Example 29 on p. 81), as selective LSD1 inhibitor.

WO 2017/02767844 discloses the p-toluenesulfonic acid salt of 1-((4-(methoxymethyl)-4-(((1R,2S)-2-phenylcyclopropylamino)methyl)piperidin-1-yl)methyl)cyclobutanecarboxylic acid

LSD1 inhibitors and methods for making them are for example disclosed in WO 2013/0220477, particularly examples 1-166 (pages 44 to 114 of corresponding EP2743256), in particular N-[4-[2-[(cyclopropylmethylamino)methyl]cyclopropyl]phenyl]-1-methyl-pyrazole-4-carboxamide (Ex. 163) which are incorporated in their entirety herein.
LSD1 inhibitors and methods for making them are for example disclosed in WO 2011/1316972, particularly examples 1-21 (pages 90 to 103), which are incorporated in their entirety herein.
LSD1 inhibitors and methods for making them are for example disclosed in WO 2013/0573224, particularly examples 1-108 (pages 155 to 191), which are incorporated in their entirety herein.
Particular LSD1 inhibitors described in WO 2013/0573224 are provided in Table 1.
TABLE 1Particular LSD1 inhibitors disclosed in WO 2013/0573224.Example No ofWO 2013/0573224Substance nameStructure 1N1-((trans)-2-phenylcyclopropyl) cyclohexane-1,4-diamine  5(trans)-N1-((1R,2S)-2- phenylcyclopropyl) cyclohexane-1,4-diamine 15(R)-1-(4-(((trans)-2- phenylcyclopropyl)amino) cyclohexyl)pyrrolidin-3-amine 174-(aminomethyl)-N-((trans)-2- phenylcyclopropyl) cyclohexanamine 18N1-((trans)-2-phenylcyclopropyl) cyclohexane-1,3-diamine 19N1-((trans)-2-phenylcyclopropyl) cyclobutane-1,3-diamine 20N1-((trans)-2-phenylcyclopropyl)- 2,3-dihydro-1H-indene-1,3-diamine 22N1-methyl-N4-((trans)-2- phenylcyclopropyl) cyclohexane-1,4-diamine 26N1-((trans)-2-(4- bromophenyl)cyclopropyl) cyclohexane-1,4-diamine 27N1-(2-(o-tolyl)cyclopropyl) cyclohexane-1,4-diamine 29N1-(2-(4- methoxyphenyl)cyclopropyl) cyclohexane-1,4-diamine 31N1-(2-(2-fluorophenyl)cyclopropyl) cyclohexane-1,4-diamine 33N1-(2-(naphthalen-2- yl)cyclopropyl) cyclohexane-1,4-diamine 50N-(4′-((trans)-2-((4- aminocyclohexyl)amino) cyclopropyl)-[1,1′-biphenyl]-3-yl)- 2-cyanobenzenesulfonamide 56N1-((trans)-2-(4-(pyridin-3- ylmethoxy)phenyl)cyclopropyl) cyclohexane-1,4-diamine
A more particular LSD1 inhibitor described in WO 2013/0573224 is (trans)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine [CAS Reg. No. 1431304-21-0]

corresponding to Example 5 therein, and pharmaceutically acceptable salts thereof. This compound is also known as ORY-1001.
It has been determined that additive or synergistic effects in inhibiting the growth of cancer cells in vitro and in vivo can be achieved by administering LSD1 inhibitors or pharmaceutically acceptable salts thereof in combination with certain other specific agents. The combination and methods may be useful in the treatment of neoplastic diseases such as cancer.
Accordingly, present invention provides combinations for use in the treatment of neoplastic diseases in a mammal comprising a LSD1 inhibitor or a pharmaceutically acceptable salt thereof, and one or more active pharmaceutical ingredient(s) selected from Table 2 or pharmaceutically acceptable salts thereof.
TABLE 2Active pharmaceutical ingredients suitable to be combined with LSD1 inhibitors.Mode ofCASLiteratureCompoundINNActionSystematic NameNumberReferenceABT-199VenetoclaxBCL24-[4-[[2-(4-1257044-WOinhibitorChlorophenyl)-4,4-40-82010/13858845 dimethylcyclohex-1-en-1-yl]methyl]piperazin-1-yl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamideABT-263NavitoclaxBCL24-(4-{[2-(4- 923564-USinhibitorChlorophenyl)-5,5-51-62007/002713546dimethyl-1-cyclohexen-1-yl]methyl}-1-piperazinyl)-N-[(4-{[(2R)-4-(4-morpholinyl)-1-(phenylsulfanyl)-2-butanyl]amino}-3-[(trifluoromethyl)sulfonyl]phenyl)sulfonyl]benzamideABT-737BCL24-[4-[[2-(4- 852808-WOinhibitorchlorophenyl)phenyl]04-92005/04959447 methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamideABT-888VeliparibPARP2-((R)-2- 912444-USinhibitorMethylpyrrolidin-2-yl)-00-92006/0229289481H-benzimidazole-4-carboxamideACY-1215RicolinostatHDAC2-(diphenylamino)-N-[7-1316214-WOinhibitor(hydroxyamino)-7-52-42011/09121349 oxoheptyl]-5-pPyrimidinecarboxamideBelinostatBelinostatHDAC(22E)-N-Hydroxy-3-[3- 866323-WO(pan-(phenylsulfamoyl)phenyl]14-02009/04051750 HDAC)prop-2-enamideinhibitorBendamustineBendamustineDNA4-[5-[Bis(2- 16506-DDalkylatingchloroethyl)amino]-1-27-7 15987751agentmethylbenzimidazol-2-yl]butanoic acidBGJ398InfigratinibFGFR3-(2,6-dichloro-3,5- 872511-WOkinasedimethoxyphenyl)-1-(6-34-72006/00042052 inhibitor((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylureaBMS-Notch(2R,3S)-N-[(3S)-1-1401066-WO906024signalingMethyl-2-oxo-5-phenyl-79-22012/12935353 inhibitor2,3-dihydro-1H-1,4-benzodiazepin-3-yl]-2,3-bis(3,3,3-trifluoropropyl)succinamideCarboplatinCarboplatinDNAcis- 41575-ESalkylatingdiammine(cyclobutane-94-4 54415954agent1,1-dicarboxylate-(DNAO,O′)platinum(II)linker)CGK 733ATM/ATR α-Phenyl-N-[2,2,2- 905973-WOkinasetrichloro-1-[[[(4-fluoro-89-92007/01563255 inhibitor3-nitrophenyl)amino]thioxomethyl]amino]ethyl]benzeneacetamideCisplatinCisplatinDNA(SP-4-2)- 15663-Rosenbergalkylatingdiamminedichloroplatinum 27-1B. et al.56agent(II)(DNAlinker)CPI-169EZH2N-[(1,2-dihydro-4-1450655-WOinhibitormethoxy-6-methyl-2-76-12013/12010457 (EZH1/2oxo-3-pyridinyl)methyl]-inhibitor)1-[1-[1-(ethylsulfonyl)-4-piperidinyl]ethyl]-2-methyl-1H-indole-3-carboxamideCPI-203BET(6S)-4-(4-chlorophenyl)-1446144-WOinhibitor2,3,9-trimethyl-6H-04-22014/13458358 (BRD2/3/thieno[3,2-4f][1,2,4]triazolo[4,3-inhibitor)a][1,4]diazepine-6-acetamideDocetaxelDocetaxelanti-1,7β,10β-trihydroxy-9- 114977-EPmitoticoxo-5β,20-epoxytax-11-28-5 25373859agentene-2α,4,13α-triyl 4-(TUBB1acetate 2-benzoate 13-stabilizer){(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate}DoxorubicinDoxorubicintopoisomerase(7S,9S)-7- 23214-DEinhibitor[(2R,4S,5S,6S)-4-amino-92-82510866605-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dioneEPZ-DOT1L7-[5-Deoxy-5-[[3-[[[[4-1338466-Daigle S. R.004777inhibitor(1,1-77-5et al.61dimethylethyl)phenyl]amino]carbonyl]amino]propyl](1-methylethyl)amino]-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineEPZ005687EZH21-cyclopentyl-N-[(1,2-1396772-WOinhibitordihydro-4,6-dimethyl-2-26-12012/11881262 oxo-3-pyridinyl)methyl]-6-[4-(4-morpholinylmethyl)phenyl]-1H-indazole-4-carboxamideEPZ-5676PinometostatDOT1L5′-deoxy-5′-[[cis-3-[2-[6-1380288-WOinhibitor(1,1-dimethylethyl)-1H-87-82012/07538163 benzimidazol-2-yl]ethyl]cyclobutyl](1-methylethyl)amino]-adenosineEPZ-6438TazemetostatEZH2N-[(1,2-dihydro-4,6-1403254-WOinhibitordimethyl-2-oxo-3-99-82012/14250464 pyridinyl)methyl]-5-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-4-methyl-4′-(4-morpholinylmethyl)-[1,1′-biphenyl]-3-carboxamideErlotinibErlotinibtyrosineN-(3-ethynylphenyl)-6,7- 183321-WOkinasebis(2-methoxyethoxy)74-69630347 A1inhibitorquinazolin-4-amineEtoposideEtoposidetopoisomerase4′-Demethyl- 33419-CHinhibitorepipodophyllotoxin 9-42-0 51457865[4,6-O-(R)-ethylidene-beta-D-glucopyranoside],4′-(dihydrogenphosphate)FLI 06NotchCyclohexyl 1,4,5,6,7,8- 313967-WOsignalinghexahydro-2,7,7-18-92013/17882166 inhibitortrimethyl-4-(4-nitrophenyl)-5-oxo-3-quinolinecarboxylateFluorouracilFluorouracilthymidylate5-Fluoro-1H,3H-51-21-8U.S. Pat No.synthasepyrimidine-2,4-dione2,802,00567inhibitorGDC-0449VismodegibHedgehog2-Chloro-N-(4-chloro-3- 879085-WOpathwaypyndin-2-ylphenyl)-4-55-92006/02895868 inhibitormethylsulfonylbenzamideGemcitabineGemcitabinenucleoside4-amino-1-(2-deoxy-2,2- 95058-GBanalogdifluoro-β-D-erythro-81-4213642569pentofuranosyl)pyrimidin-2(1H)-onGSK126EZH2N-[(1,2-dihydro-4,6-1346574-WOinhibitordimethyl-2-oxo-3-57-92011/14032470 pyridinyl)methyl]-3-methyl-1-[(1S)-1-methylpropyl]-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamideGSK132472BET4-[(2S,4R)-1-acetyl-4-1300031-WO6Ainhibitor[(4-chlorophenyl)amino]-52-02011/05484371 (I-BET726)(BRD2/3/1,2,3,4-tetrahydro-2-4methyl-6-quinolinyl]-inhibitor)benzoic acidGSK343EZH2N-[(1,2-dihydro-6-1346704-WOinhibitormethyl-2-oxo-4-propyl-33-32011/14032572 (EZH1/23-pyridinyl)methyl]-1-(1-inhibitor)methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamideGSK-J1demethylaseN-[2-(2-Pyridinyl)-6-1373422-WOinhibitor(1,2,4,5-tetrahydro-3H-3-53-72012/05239073 (JMJD3/benzazepin-3-yl)-4-UTXpyrimidinyl]-β-alanineinhibitor)GSK121015BET7,3,5-dimethyl-4-1300031-WO1Ainhibitorisoxazolyl-1,3-dihydro-8-49-52011/05484371  (I-BET151)(BRD2/3/methoxy-1-[1R-1-(2-4pyridinyl)ethyl]-2H-inhibitor)imidazo[4,5-c]quinolin-2-oneIrinotecanIrinotecantopoisomerase(S)-4,11-diethyl- 100286-U.S. Pat. No.inhibitor3,4,12,14-tetrahydro-4-90-66,121,45174hydroxy-3,14-dioxo1H-pyrano[3′,4′:6,7]-indolizino[1,2-b]quinolin-9-yl-[1,4′bipiperidine]-1′-carboxylate(+)-JQ1BET(S)-tert-butyl 2-(4-(4-1268524-WOinhibitorchlorophenyl)-2,3,9-70-42011/14365175 (BRD2/3/trimethyl-6H-thieno[3,2-4f][1,2,4]triazolo[4,3-inhibitor)a][1,4]diazepin-6-yl)acetateLapatinibLapatinibtyrosineN-[3-chloro-4-[(3- 231277-WOkinasefluorophenyl)methoxy]92-2 99/3514676inhibitorphenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amineLDE225SonidegibHedgehogN-[6-[(2S,6R)-2,6- 956697-WOpathwayDimethylmorpholin-4-53-32010/03348177 inhibitoryl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamideLY2603618ChkN-[5-bromo-4-methyl-2- 911222-WOinhibitor[(2S)-2-45-22006/10526278 morpholinylmethoxy]phenyl]-N′-(5-methyl-2-pyrazinyl)-ureaLY-NotchN-[(1S)-2-[[(7S)-6,7-1421438-WO3039478signalingdihydro-5-(2-81-42013/01608179 inhibitorhydroxyethyl)-6-oxo-5H-pyrido[3,2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4,4,4-trifluoro-butanamideMenadioneMenadione1,4-2-Methylnaphthalene-58-27-5U.S. Pat No.naphthoquinone1,4-dione2,331,72580analogueMethotrexateMethotrexatefolic acid(2S)-2-[(4-{[(2,4-59-05-2U.S. Pat No.inhibitorDiaminopteridin-6-2,512,572 (DHFRyl)methyl](methyl)amino}inhibitor)benzoyl)amino]pentanedioic acidMK-0752Notchcis-4-[(4- 471905-WOsignalingchlorophenyl)sulfonyl]-41-62002/08143581 inhibitor4-(2,5-difluorophenyl)-(gammacyclohexanepropanoicsecretaseacidinhibitor)MLN8237AlisertibAurora A4-[[9-chloro-7-(2-fluoro-1028486-WOkinase6-methoxyphenyl)-5H-01-22008/06352582 inhibitorpyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-benzoic acidMS 436BET4-[(1E)-2-(2-amino-4-1395084-WOinhibitorhydroxy-5-25-92012/11617083 (BRD2/3/methylphenyl)diazenyl]-4N-2-pyridinyl-inhibitor)benzenesulfonamideNutlin-3ANutlin-3AMDM22-Piperazinone, 4- 675576-USinhibitor[[(4S,5R)-4,5-bis(4-98-42005/028280384chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-ObatoclaxObatoclaxBCL22-(2-((3,5-Dimethyl-1H- 803712-WOinhibitorpyrrol-2-yl)methylene)-67-62004/10632885 3-methoxy-2H-pyrrol-5-yl)-1H-indoleOTX015BET(6S)-4-(4-chlorophenyl)- 202590-U.S. Pat No.inhibitorN-(4-hydroxyphenyl)-98-55,712,27486(BRD2/3/2,3,9-trimethyl-6H-4Thieno[3,2-inhibitor)f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamidePaclitaxelPaclitaxelanti-(2α,4α,5β,7β,10β,13α)- 33069-EPmitotic4,10-Bis(acetyloxy)-13-62-4 25373987agent/{[(2R,3S)-3-TUBB(benzoylamino)-2-stabilizerhydroxy-3-phenylpropanoyl]oxy}-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-ylbenzoatePanobinostatPanobinostatHDAC(2E)-N-hydroxy-3-[4- 404950-WO(pan-({[2-(2-methyl-1H-indol-80-72002/02257788 HDAC)3-inhibitoryl)ethyl]amino}methyl)phenyl]acrylamidePemetrexedPemetrexedfolic acid(2S)-2-{[4-[2-(2-amino- 137281-EPinhibitor4-oxo-1,7-23-3 43267789(TYMS/dihydropyrrolo[2,3-DHFR/GARTd]pyrimidin-5-inhibitor)yl)ethyl]benzoyl]amino}pentanedioic acidPF-c-Met4-[1-(6- 956905-US04217903inhibitorquinolinylmethyl)-1H-27-42007/0265272901,2,3-triazolo[4,5-b]pyrazin-6-yl]-1H-pPyrazole-1-ethanolPF-3084014Notch(2S)-2-[[(2S)-6,8- 865773-USsignalingDifluoro-1,2,3,4-15-52005/021561091inhibitortetrahydro-2-(gammanaphthalenyl]amino]-N-secretase[1-[2-[(2,2-inhibitor)dimethylpropyl)amino]-1,1-dimethylethyl]-1H-imidazol-4-yl]pentanamidedihydrobromideSAHAVorinostatHDACsuberanilohydroxamic 149647-WOinhibitoracid78-993/0714892SGC 0946DOT1L1-[3-[[[(2R,3S,4R,5R)-5-1561178-Yu et al.93inhibitor(4-Amino-5-bromo-7H-17-3pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl](isopropyl)amino]propyl]-3-[4-(2,2-dimethylethyl)phenyl]ureaSNDX-275EntinostatHDACN-[[4-[[(2- 209783-JPinhibitoraminophenyl)amino]80-21015246294 carbonyl]phenyl]methyl]-carbamic acid 3-pyridinylmethyl esterTaladegibTaladegibHedgehog4-fluoro-N-methyl-N-[1-1258861-WOpathway[4-(1-methyl-1H-20-92010/14791795 inhibitorpyrazol-5-yl)-1-(smoothenedphthalazinyl]-4-inhibitor)piperidinyl]-2-(trifluoromethyl)-benzamideTemozolomideTemozolomideDNA4-methyl-5-oxo- 85622-DEalkylating2,3,4,6,8-93-1323125596agentpentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamideTopotecanTopotecantopoisomerase(S)-10- 123948-EPinhibitor[(dimethylamino)methyl]-87-8 321122974-ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino [1,2-b]quinoline-3,14(4H,12H)-dionemonohydrochlorideTW-37BCL2N-[4-[[2-(1,1- 877877-WOinhibitordimethylethyl)phenyl]35-52006/02377898 (BCL2,sulfonyl]phenyl]-2,3,4-BCL-xl,trihydroxy-5-[[2-(1-MCL-1methylethyl)phenyl]methyl]-inhibitor)benzamideVincristineVincristineanti-(3aR,3a1R,4R,5S,5aR,10bR)-57-22-7BEmitoticMethyl 4-acetoxy- 62407699agent3a-ethyl-9-((5S,7S,9S)-5-(TUBB2ethyl-5-hydroxy-9-destabilizer)(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate
The structures of the compounds of Table 2 are as follows:
